The objective of this proposal is to determine the cellular basis for changes in pituitary responsiveness to gonadotropin releasing hormone in the normal aging rat. The anterior pituitary produces hormones which, in turn, regulate major physiological functions including reproduction, carbohydrate and salt metabolism, and growth. A large body of information suggests that changes in these functions during senescence is correlated with changes in pituitary responsiveness to hypothalamic releasing hormones. The present study has been designed to quantitate the contribution of specific cellular changes which result in this altered pituitary responsiveness to gonadotropin releasing hormone. An understanding of these functions will be particularly useful since it will explain the basisfor physiological changes in gonadotropin levels and biological activity. It is probable that altered responsiveness is mediated through either molecular changes in GnRH receptor levels, changes in coupling of the receptor to the mechanism of stimulation, or changes in gonadotropin processing and secretion. Analysis of these indivdual steps in normal aging rats will result in the development of a cellular model for altered pituitary responsiveness. Such a model will stimulate experimental testing and suggest clinical manipulations in research related to the aging process and the problems of the aged.